Morphology and hemodynamics in isolated common iliac artery aneurysms impacts proximal aortic remodeling

Objective- Isolated common iliac artery aneurysms (CIAA) are rare. Their prognosis and influence on aortoiliac blood flow and remodeling are unclear. We evaluated the hypotheses that morphology at and distal to the aortic bifurcation, together with the associated hemodynamic changes, influence both the natural history of CIAA and proximal aortic remodeling. Approach and Results- Twenty-five isolated CIAAs (15 intact, 10 ruptured), in 23 patients were reconstructed and analyzed with computational fluid dynamics: all showed abnormal flow. Then we studied a series of 24 hypothetical aortoiliac geometries in silico with varying abdominal aortic deflection and aortic bifurcation angles: key findings were assessed in an independent validation cohort of 162 patients. Wall shear stress in isolated unilateral CIAAs was lower than the contralateral common iliac artery, 0.38±0.33 Pa versus 0.61±0.24 Pa, inversely associated with CIAA diameter ( P<0.001) and morphology (high shear stress in variants distal to a sharp kink). Rupture usually occurred in regions of elevated low and oscillatory shear with a wide aortic bifurcation angle. Abdominal aortas deflected towards the CIAA for most unilateral isolated CIAAs (14/21). In silico, wider bifurcation angles created high focal regions of low and oscillatory shear in the common iliac artery. The associations of unilateral CIAA with aortic deflection and common iliac artery diameter with bifurcation angle were confirmed in the validation cohort. Conclusions- Decreasing wall shear stress is strongly associated with CIAA progression (larger aneurysms and rupture), whereas abnormal blood flow in the CIAA seems to promote proximal aortic remodeling, with adaptive lateral deflection of the abdominal aorta towards the aneurysmal side

Surgical management of life threatening events caused by intermittent aortic insufficiency in a native valve: case report

We describe a case of a patient admitted with apparent life threatening events characterized by hypotension and bradycardia. The patient was ultimately found to have intermittent severe aortic insufficiency. Upon surgical exploration, abnormalities were discovered in the aortic valve, which had a small left coronary cusp with absence of the nodulus of Arantius. Following surgical repair of the valve, aimed at preventing the small cusp from becoming stuck in the open position, the patient has remained episode free for over one year

Newsprint coverage of smoking in cars carrying children : a case study of public and scientific opinion driving the policy debate

Acknowledgements Date of Acceptance:17/10/2014 Acknowledgements: This project was funded by Cancer Research UK (MC_U130085862) and the Scottish School of Public Health Research. Cancer Research UK and the Scottish School of Public Health Research was not involved in the collection, analysis, and interpretation of data, writing of the manuscript or the decision to submit the manuscript for publication. Shona Hilton, Karen Wood, Josh Bain and Chris Patterson are funded by the UK Medical Research Council as part of the Understandings and Uses of Public Health Research programme (MC_UU_12017/6) at the MRC/CSO Social and Public Health Sciences Unit, University of Glasgow. We thank Alan Pollock who provided assistance with coding.Peer reviewedPublisher PD

Microscopy in forensic science

This chapter examines the use of electron microscopy, atomic force microscopy and other analytical techniques in forensic investigation and research. These tools can be used to enhance examination of human remains and trace evidence to improve understanding of cause of death, victim identification or post mortem interval.A police-designed scenario is used to highlight trace evidence such as glass, gun shot residue and paint. The validity of forensic techniques is discussed, with reference to international standards, repeatability, and false convictions. Ballistic evidence is used to highlight the complexities in evidence interpretation, including manufacturing variability, environmental effects and likelihood ratios.The use of scanning electron microscopy (SEM), atomic force microscopy (AFM) and other techniques in the development of forensic research is showcased, with particular examples from the field of fingerprints. Examples include improvements in the development of fingermarks from difficult surfaces, interaction of evidence types, and added intelligence from the crime scene, such as forensic timeline or gender of perpetrator

Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine

This article has been made available through the Brunel Open Access Publishing Fund.Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 μg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation

FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells

Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours

Antiferromagnetic spintronics

Antiferromagnetic materials are magnetic inside, however, the direction of their ordered microscopic moments alternates between individual atomic sites. The resulting zero net magnetic moment makes magnetism in antiferromagnets invisible on the outside. It also implies that if information was stored in antiferromagnetic moments it would be insensitive to disturbing external magnetic fields, and the antiferromagnetic element would not affect magnetically its neighbors no matter how densely the elements were arranged in a device. The intrinsic high frequencies of antiferromagnetic dynamics represent another property that makes antiferromagnets distinct from ferromagnets. The outstanding question is how to efficiently manipulate and detect the magnetic state of an antiferromagnet. In this article we give an overview of recent works addressing this question. We also review studies looking at merits of antiferromagnetic spintronics from a more general perspective of spin-ransport, magnetization dynamics, and materials research, and give a brief outlook of future research and applications of antiferromagnetic spintronics.Comment: 13 pages, 7 figure

What traits are carried on mobile genetic elements, and why?

Although similar to any other organism, prokaryotes can transfer genes vertically from mother cell to daughter cell, they can also exchange certain genes horizontally. Genes can move within and between genomes at fast rates because of mobile genetic elements (MGEs). Although mobile elements are fundamentally self-interested entities, and thus replicate for their own gain, they frequently carry genes beneficial for their hosts and/or the neighbours of their hosts. Many genes that are carried by mobile elements code for traits that are expressed outside of the cell. Such traits are involved in bacterial sociality, such as the production of public goods, which benefit a cell's neighbours, or the production of bacteriocins, which harm a cell's neighbours. In this study we review the patterns that are emerging in the types of genes carried by mobile elements, and discuss the evolutionary and ecological conditions under which mobile elements evolve to carry their peculiar mix of parasitic, beneficial and cooperative genes